Myeloid Derived Suppressor Cells Inhibit Natural Killer Cells in Patients with Hepatocellular Carcinoma via the NKp30 Receptor

By Bastian Hoechst, T. Voigtlaender, Lars A. Ormandy, Jaba Gamrekelashvili, F. Zhao, H. Wedemeyer, F. Lehner, M. Manns, T. Greten, F. Korangy. Hepatology, 2009

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Several immune suppressive mechanisms that evade the host immune response have been described in patients with hepatocellular carcinoma (HCC); one of these mechanisms is expansion of myeloid‐derived suppressor cells (MDSCs). MDSCs have been shown to inhibit T cell responses in tumor‐bearing mice, but little is known about these cells in humans. Here, we have analyzed and characterized the effect of MDSCs on the innate immune system, in particular, their interaction with natural killer (NK) cells in patients with HCC. MDSCs from patients with HCC inhibited autologous NK cell cytotoxicity and cytokine secretion when cultured together in vitro. This suppression was dependent on cell contact, but did not rely on the arginase activity of MDSCs, which is a hallmark function of these cells. However, MDSC‐mediated inhibition of NK cell function was dependent mainly on the NKp30 on NK cells. Conclusion: Our study suggests a new role for MDSCs in patients with HCC in disarming the innate immune system and further contributing to the immune suppressor network in these patients. These findings have important implications when designing immunotherapy protocols. (HEPATOLOGY 2009.)

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/b6c9b28edb19daa5b0750abd57d4fb52c85601a0

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Citations in the corpus

Advances in immunotherapy for hepatocellular carcinoma (2021, background): “I.M. receives funding from MINECO SAF2014-52361-R and SAF 2017- 83267-C2-1R; Worldwide Cancer Research Grant (15-1146); the Asociacion Española Contra el Cancer (AECC) Foundation under grant GCB15152947MELE; and the European Union’s Horizon 2020 Program (grant agreement no. 635122 PROCROP).”
Coordinated regulation of myeloid cells by tumours (2012, background): “MDSCs also decrease the number and inhibit the function of mouse and human NK cells, mostly through membrane contact-dependent mechanisms (that is, through membrane-bound TGFβ (in the case of mouse MDSCs) and through interaction with the NK cell receptor NKp30 (also known as NCR3)”
The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer (2016, background): “In HCC, MDSCs inhibit not only the adaptive but also the innate immune response (142) and are capable of inducing immunosuppressive Tregs (104).”